The value of vaccines – in terms of preventing suffering, controlling outbreaks and eradicating virulent strains in the health care systems – is enormous. Unfortunately, the availability and use of prophylaxis vaccines in Asia Pacific is less than optimal for various reasons.
Drawing from available literature, Quintiles’ data and our experiences in helping companies develop new and better vaccines – including our interactions with leading investigators involved in infectious disease research – we detail in this paper the top five infectious diseases in Asia Pacific for which vaccinations offer the greatest benefit in terms of improved health and value. Our focus is on disease prevalence, transmission and clinical research issues.
Influenza: In recent years, the regional emergence of novel viruses such as SARS, H5N1 and H7N9 have created epidemics that raised global concerns. Despite the generation and global seeding of seasonal influenza viruses and initiatives by the World Health Organization (WHO), governments and non-governmental organizations to expand influenza awareness, the use of seasonal influenza vaccines still remains below expected baselines. Adding to the complexity, influenza viruses are polymorphic by nature which means manufacturers of vaccines need to cope with changes in viral strands in vaccines with speed, precision and volume.
Taking the economic status of the countries within this region as a gauge, countries fall into two categories – developed and developing. Influenza vaccines are not reimbursed by ministries of health in Asia Pacific; developed countries such as Japan, Australia, Singapore and New Zealand have insurance coverage instead over such vaccinations and, as such, their residents are usually vaccinated against influenza and are protected.
Unfortunately, developing countries experience a shortage of influenza vaccines and many suburban towns and villages would not even have knowledge of such infections. Specifically for influenza virus vaccine studies, Quintiles has observed higher recruitment rates from satellite sites located in rural areas of developing countries.
Hepatitis B Virus (HBV): Recent reports have revealed that Asia Pacific has the world’s highest rates of hepatitis B infections  even though HBV vaccines were introduced to children and adolescents in the 1990s. Based on observations, HBV vaccination has now been better enforced in newborns over the years and has had a large impact on acute HBV infection within the region. However, it was also observed that it has much lesser impact on chronic HBV diseases which prerequisites hepatocellular carcinoma, a primary malignancy of the liver.
Quintiles’ experiences with local hospitals and investigators reveal a mild improvement in awareness among the general Asian population in the availability this vaccine, rates of infection and modes of transmission. Nonetheless, a significant number of people are still unaware of their chronic condition; nor are they aware that transmission is possible between mothers and infants or through any contact with infected patients. Vaccination may have been introduced into most of Asia’s immunization schedule since the 1990s but there are still multiple groups of people who are not immunized or have not addressed their age-specific decline in immunogenicity – thus the need for booster vaccines as adults.
With Asia Pacific being home to the highest population of HBV infected patients, it is relatively common to find someone living with an HBV infected patient. Frequent testing and screening is necessary to prevent the spread of the disease – yet many developing areas within the region simply do not have the access to such medical supplement/support.
Pneumococcal Virus (PCV): The burden of PCV-related disease is huge globally, and especially so in India and South Asia; it has been increasing throughout Asia Pacific with Streptococcus pneumoniae as one of the most popular culprit in Asia subjects . It is estimated that the S. pneumoniae virus is responsible for 15 to 50 percent of Community Acquired Pneumonia (CAP); between 30 to 50 percent of all cases of acute otitis media; and a significant proportion of bacteremia and bacterial meningitis. 
Data supports the conclusion that PCV-related disease is an important cause of child morbidity and mortality in South Asia. Multivalent vaccines were developed years ago, yet some developing countries within the region still do not have PCV vaccines in their national immunization programs. Many times, subjects are not able to obtain the vaccines due to cost and accessibility.
Rotavirus: Rotavirus takes the lives of thousands Asian children under five each year, accounting for more than 40 percent of the global total of rotavirus deaths . It is estimated that approximately 35 percent of Asian children hospitalized with acute diarrheal illness are infected with rotavirus.
Studies in Asia Pacific indicate that rotavirus vaccines are safe and effective against severe rotavirus disease and are a cost-effective intervention. The high burden of rotavirus disease in Asian children, coupled with the power of rotavirus vaccines to prevent childhood deaths and hospitalizations, underscores the vast potential for the introduction of rotavirus vaccines in Asian countries to save children’s lives.
However, this vaccine is not widely available in Asia Pacific and is expensive for a significant part of the Asian population. Many ministries of health recommend it to parents, but it is not compulsory – which worries epidemiologists. The benefits and risks of these vaccines and diseases also were frequently understated to parents, which often led parents to perceive rotavirus vaccines as an option rather than a need. The message is further distorted when certain governments, because of constraints on health care spending, do not fully subsidize the vaccine, e.g. China, India and Southeast Asian countries. As such, these factors make rotavirus vaccine studies in Asia Pacific extremely attractive.
Human Papillomavirus (HPV): HPV causes cervical cancer, which is the fourth most common cancer in women in Asia Pacific . Virtually all cervical cancer cases (99 percent) are linked to genital infection with HPV; it is the most common viral infection of the reproductive tract. HPV can also cause other types of anogenital cancer, head and neck cancers, and genital warts in both men and women. HPV infections are transmitted through sexual contact.
HPV vaccination is often recommended for females between 13-26 years of age before becoming sexually active in order to maximize the benefit of the vaccines. Nonetheless, studies also indicate that HPV vaccines can still be beneficial to females who are exposed to HPV or are sexually active already, but lesser than the former population groups. In most developed countries, the benefits of HPV vaccines are relatively well understood and women in these countries are more willing to get such vaccines from a gynecologist despite the vaccines being expensive. Some developed countries such as Singapore and Australia also have government subsidies to promote HPV vaccination.
Though immunization rates have increased gradually over the years, attitudes within conservative Asian cultures and religions still continue to discourage individuals from making appointments for relevant screenings or interacting with gynecologists to receive such vaccines. Based on observation, we believe that affordability and availability of HPV and awareness of HPV's links to cervical cancer have much room for improvement.
Observations on Asia Pacific vaccine development technology
Vaccine developers in the region have traditionally targeted local/regional markets with “me-too”-type products, emphasizing potential cost savings over global brands. More recently, however, we have begun to see a shift in strategy as many have begun to target global markets – seeking product registration in the United States, the European Union and other Western regulatory agencies.
In addition, several manufacturers have sought WHO pre-qualification for specific vaccines, intending to target the Global Alliance for Vaccines and Immunization (GAVI, a public-private global health partnership formed to increase access to immunization in poor countries) and health agencies of developing countries in the region, such as South Korea and China.
There has been exponential growth in biotechnology expertise and sophistication among Asia Pacific vaccine developers in recent years. Some of the vaccine technologies (e.g. DNA plasmids and delivery systems; T-cell targeting, etc.) and target profiles rival any from the West; we anticipate rapid translation of these platforms to the clinic.
Willingness of parents to enroll children to vaccine studies
Having conducted multiple studies within the region, we established a pool of knowledge and an information network that allowed us to well understand trends in the region. Our observations indicate that recruitment of healthy infants and children from countries such as South Korea, Taiwan, Singapore and Malaysia are usually challenging, as their parents or guardians are less willing to participate in clinical studies.
This was supported by a survey conducted by the Korean Journal of Pediatrics (Rhim JW, 2006) which showed 51.7 percent  resistance against participation in vaccine clinical studies unconditionally. Motivation to join studies will hence require an innovative and advantageous compound to the current standard of care available in the country. Based on our assessment of the local landscape, we observed higher number of vaccines clinical studies conducted among adults.
In contrast, we observed high enrolment and willingness for subjects’ parents or guardians in other Asian countries such as the Philippines, Vietnam, Thailand, China and India. Southeast Asia countries such as Vietnam, the Philippines and Thailand are popular sites for healthy subject vaccine studies within the region. Their unique site outreach structure allowed sites to offer experienced team members along with high pediatric enrollment rates at low cost.
What differentiates Asia Pacific in vaccine development?
Key characteristics by selected countries
Healthy subject vaccine experience by study population types in Asia
Figure 2 illustrates the number of healthy volunteer vaccine experience by study population types in a few selected countries. India, Vietnam, the Philippines and Thailand typically conduct more pediatric healthy volunteers vaccine trials. The common characteristic of these four countries is that both coverage of basic vaccines and reimbursement levels for vaccines in general are lower than some East Asia countries.
Though we understand there is much more resistance to participate in infants or children vaccine studies in East Asia countries, there are still cases of exception. Taiwan for instance, has conducted more pediatric vaccine studies involving innovative vaccines such as combined vaccine products or Influenza vaccines. Out of 36 vaccine clinical trials with pediatric population (18 years and below), 20 of these studies included the use of combined vaccine products or Influenza vaccines in Taiwan.
In China and India, we noted that the number of healthy subject studies for pediatrics-only and adults-only are comparable. This suggests that the country may be receptive to conducting healthy subject vaccine studies for both population groups. However these countries would have a more stringent regulatory process in approving the clinical studies.
Types of site-settings where vaccine clinical studies could be conducted
One advantage to Southeast Asia and India as locations to conduct pediatric healthy subject studies is that the key investigator from the main site – usually a hospital or specialized hospital for infectious disease prevention – has access to other satellite sites and schools to boost recruitment if required.
For China, instead of reaching out to hospitals, healthy subject vaccine studies are conducted in the CDCs at the provincial level. Multiple satellite sites at the municipal or county level would be activated to recruit healthy subjects; in other East Asian countries recruitment activities are carried out mainly at the hospital level.
Before conducting any vaccine studies with healthy subjects, key feasibility considerations must be evaluated to determine which countries are most suited. These include the level of reimbursements for vaccines; targeted study population type; seasonality of the disease (such as Influenza vaccine studies); and each country’s standard of care. All of these factors and more are crucial to timely recruitment and successful completion of vaccine studies involving healthy subjects.
About the Authors
Angela Chen Si Ting
Associate Therapeutic Strategy Lead
Vaccines and Infectious Diseases
Therapeutic Science and
Strategy Asia Pacific
Adeline Sng Bi Lin
Regional Feasibility Lead
Vaccines and Infectious Diseases
Clinical Planning and
Analytics Asia Pacific
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